Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Nature. 2018 Mar 1;555(7694):107-111. doi: 10.1038/nature25757. Epub 2018 Jan 24.
Long noncoding RNAs (lncRNAs) are emerging as key parts of multiple cellular pathways, but their modes of action and how these are dictated by sequence remain unclear. lncRNAs tend to be enriched in the nuclear fraction, whereas most mRNAs are overtly cytoplasmic, although several studies have found that hundreds of mRNAs in various cell types are retained in the nucleus. It is thus conceivable that some mechanisms that promote nuclear enrichment are shared between lncRNAs and mRNAs. Here, to identify elements in lncRNAs and mRNAs that can force nuclear localization, we screened libraries of short fragments tiled across nuclear RNAs, which were cloned into the untranslated regions of an efficiently exported mRNA. The screen identified a short sequence derived from Alu elements and bound by HNRNPK that increased nuclear accumulation. Binding of HNRNPK to C-rich motifs outside Alu elements is also associated with nuclear enrichment in both lncRNAs and mRNAs, and this mechanism is conserved across species. Our results thus identify a pathway for regulation of RNA accumulation and subcellular localization that has been co-opted to regulate the fate of transcripts with integrated Alu elements.
长链非编码 RNA（lncRNA）正在成为多种细胞途径的关键组成部分，但它们的作用模式以及序列如何决定这些模式仍不清楚。lncRNA 往往在核部分富集，而大多数 mRNA 则明显在细胞质中，尽管有几项研究发现，在各种细胞类型中，数百种 mRNA 被保留在核内。因此，可以想象，促进核富集的一些机制在 lncRNA 和 mRNA 之间是共享的。在这里，为了鉴定能够迫使核定位的 lncRNA 和 mRNA 中的元件，我们筛选了覆盖核 RNA 的短片段文库，这些片段克隆到高效输出 mRNA 的非翻译区。筛选鉴定出一个源自 Alu 元件的短序列，该序列与 HNRNPK 结合，增加核积累。HNRNPK 与 Alu 元件外的 C 丰富基序的结合也与 lncRNA 和 mRNA 的核富集有关，这种机制在物种间是保守的。因此，我们的结果确定了一种调节 RNA 积累和亚细胞定位的途径，该途径被用来调节整合了 Alu 元件的转录物的命运。
